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Perhaps one of the most feared conditions associated with aging is dementia — an impaired ability to think or recall. The most common cause is Alzheimer’s disease. Aging also may be associated with lesser — but still disruptive — thinking and memory problems, which is called mild cognitive impairment. Mild cognitive impairment is a common precursor to Alzheimer’s.

Researchers, doctors, drug and biotech companies, and medical institutions worldwide are urgently seeking to better understand the intricacies of brain function — and particularly to develop therapies to prevent or treat diseases such as Alzheimer’s and other forms of dementia.

But despite this substantial effort, no drug or therapy can beat the powerful effect that regular physical exercise has in preventing Alzheimer’s and improving brain function — even in those with Alzheimer’s.

One Mayo Clinic study showed that those who regularly engaged in moderate exercise five or six times a week in later life reduced their risk of mild cognitive impairment by 32 percent compared with more sedentary people. Those who began exercising at midlife saw a 39 percent reduction in the risk of mild cognitive impairment.

Numerous other studies have come to similar conclusions. In one study, the effect of exercise on those with memory problems was about as good as the documented benefit of donepezil (Aricept), a drug that can modestly and temporarily improve symptoms of mild cognitive decline.

It’s not entirely clear how exercise protects the brain from Alzheimer’s, but research has pointed to several important possibilities.

One reason may be increased brain volume and possibly the creation of new brain cells. Gray matter makes up the bulk of brain tissue and is the location of many important brain functions, including memory. Gray matter decreases in volume with age. In addition, an area of gray matter in the brain called the hippocampus — which is crucial for memory — progressively deteriorates in those with Alzheimer’s.

Exercise appears to preserve gray matter, the benefits of which have been directly documented with brain imaging. In one study of older adults, significant enlargement of the hippocampus was observed in those who did moderately intense exercise over the course of one year when compared with people who did only basic stretching and toning for one year. Moreover, this increased hippocampus volume was associated with improved cognition.

Limited laboratory evidence also suggests the possibility that new brain cells can be created within the critical parts of the hippocampus. Increased blood volume — suggestive of greater biological activity — has been observed in parts of the hippocampus in individuals who are physically fit. This indicates that exercise may have the potential to slow the decline of Alzheimer’s.

Another possible explanation for how exercise can help ward off dementia is the improvement in levels of brain connections of those who exercise regularly. Substances such as brain-derived neurotrophic factor (BDNF) are like fertilizer for brain cells. They have been associated with a wide variety of biochemical changes in the brain consistent with making new brain connections. Levels of BDNF circulating in the blood are lower in those with Alzheimer’s than in those who don’t have the disease. BDNF levels appear to be increased by exercise.

Improved blood vessel health also may protect the brain from dementia. Fitness is often a sign of good blood vessel health. That’s because fitness helps prevent — and is an effective therapy for — many conditions that contribute to damage and clogging of blood vessels, such as high blood pressure, diabetes and undesirable cholesterol levels.

Aging brain arteries are highly susceptible to narrowing and closure, especially the smallest of these arteries. The result of narrowing of small vessels can be seen on routine magnetic resonance imaging (MRI) as white patches (leukoaraiosis) in the brain. Blockage of small brain arteries causes potentially unnoticeable “ministrokes” that damage tiny areas of the brain. Leukoaraiosis and blood vessel closure can cause or contribute to the development of cognitive impairment and Alzheimer’s.

In people with mild cognitive impairment or Alzheimer’s, regular exercise can have a major impact on health, as it can with anyone. Research has shown that people with Alzheimer’s who exercise have less risk of potentially life-threatening problems such as falls, osteoporosis, cardiovascular disease and other age-related problems. Depression and anxiety are common problems in both diseases, and exercise can significantly improve these conditions as well. — Ronald Petersen, M.D., Ph.D., Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, Minn.